Biology:WAVE regulatory complex
The WAVE regulatory complex (WRC, SCAR complex) is a five-subunit protein complex in the Wiskott-Aldrich syndrome protein (WASP) family involved in the formation of the actin cytoskeleton through interaction with the Arp2/3 complex. The holocomplex comprises WAVE1 (also known as WASF1), CYFIP1, ABI2, Nap1 and HSPC300 in its canonical form, or orthologues of these.[1]
Composition
The proteins within the WRC form a CYFIP1-Nap1 heterodimer and a WAVE1-Abi2-HSPC300 heterotrimer,[1][2] and following interaction with Rac1, the holocomplex has been observed in a CYFIP1-Nap1-Abi2 heterotrimer subcomplex and an active WAVE1-HSPC300 heterodimer subcomplex.[3]
Function
WRC recruitment to the sites of actin nucleation events at the cell periphery is mediated by the binding of a number of ligands containing a conserved WRC interacting receptor sequence (WIRS) which binds to a conserved location shared across the surfaces of Abi2 and CYFIP1.[4] The WRC is activated by interaction with the Rac1 (via the CYFIP1 component of the complex) and Arf small GTPases[1] (such as ARF1, ARF5, and ARF6[5] ) or the similar protein ARL1,[2] which causes dissociation of the CYFIP1-Nap1-Abi2 heterotrimer at the membrane periphery.[3] This allows the V domain of the WAVE1 component to interact with the actin monomers while its CA domain interacts with the Arp2/3 complex, allowing the Arp2/3 complex to act as a nucleation core for the branching and extension of actin filaments.
References
- ↑ 1.0 1.1 1.2 "Structure and control of the actin regulatory WAVE complex". Nature 468 (7323): 533–8. November 2010. doi:10.1038/nature09623. PMID 21107423. Bibcode: 2010Natur.468..533C.
- ↑ 2.0 2.1 "WAVE regulatory complex activation by cooperating GTPases Arf and Rac1". Proceedings of the National Academy of Sciences of the United States of America 108 (35): 14449–54. August 2011. doi:10.1073/pnas.1107666108. PMID 21844371. Bibcode: 2011PNAS..10814449K.
- ↑ 3.0 3.1 "CYFIP family proteins between autism and intellectual disability: links with Fragile X syndrome". Frontiers in Cellular Neuroscience 8: 81. 27 March 2014. doi:10.3389/fncel.2014.00081. PMID 24733999.
- ↑ "The WAVE regulatory complex links diverse receptors to the actin cytoskeleton". Cell 156 (1–2): 195–207. January 2014. doi:10.1016/j.cell.2013.11.048. PMID 24439376.
- ↑ "Arf6 coordinates actin assembly through the WAVE complex, a mechanism usurped by Salmonella to invade host cells". Proceedings of the National Academy of Sciences of the United States of America 110 (42): 16880–5. October 2013. doi:10.1073/pnas.1311680110. PMID 24085844. Bibcode: 2013PNAS..11016880H.
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